Carpal tunnel syndrome (CTS) is the most common hand disorder, accounting for half a million carpal tunnel release surgeries annually in the United States. It has an immensely negative impact on national health care costs, worker productivity, and activities of daily living. Despite its impact on public health, our understandin of CTS etiology is limited. However, carpal tunnel pathomechanics is known to be an important contributor to the development of CTS. Notably, the transverse carpal ligament (TCL) plays a critical role in regulating carpal tunnel mechanics and is a potential factor in median nerve compression. The goal of this project is to explore a novel concept of the pathomorphological and pathomechanical properties of the TCL as an etiological factor of CTS. Our central hypothesis is that changes in the morphological and the mechanical properties of the TCL are pathogenic mechanisms of CTS. This hypothesis is supported by empirical observations during carpal tunnel release surgeries and preliminary data in the literature, yet it remains to be scientifically investigated. The specific aims of this project are (1) to examine the pathomorphology of the transverse carpal ligament associated with CTS using B-mode ultrasound imaging, and (2) to investigate the pathomechanics of the transverse carpal ligament associated with CTS using acoustic radiation force impulse (ARFI) ultrasound imaging. We will test the hypotheses that, in comparison to asymptomatic controls, the TCLs in CTS individuals are thicker and have a greater Young's modulus. This clinically oriented research innovatively applies ultrasound imaging technology for the identification of pathomorphological and pathomechanical markers of CTS. The results of this study will aid in the discovery of alternative pathogeneses of CTS. The noninvasive B-mode and ARFI imaging will provide convenient, cost-effective tools to screen high-risk CTS populations for prevention and to diagnose and assess the severity of CTS. In addition, critical new knowledge generated from this project will provide a foundation for a new research direction with profound occupational and clinical applications. Confirmation of our hypotheses will encourage a future large-scale clinical and epidemiological study that emphasizes carpal tunnel pathomorphology and pathomechanics as novel etiological factors of CTS. This pilot project, though developmental and exploratory, has a high benefit/cost ratio.